Lymphatic Vessel Tumors

Target Indications Include Microcystic Lymphatic Malformations, Venous Malformations and Angiofibromas Proprietary Invisicare Delivery Technology Designed to Optimize Local Skin Penetration Company Plans to Submit Investigational New Drug Applications and Initiate Clinical Testing This Year ASHBURN, Va., March 04, 2025 (GLOBE NEWSWIRE) -- Quoin Pharmaceuticals Ltd. (NASDAQ: QNRX) (the “Company” or “Quoin”), a late clinical stage, specialty pharmaceutical company focused on rare and orphan diseases, today announced it has filed U.S. and International patent applications for novel topical rapamycin (sirolimus) formulations as potential treatments for a number of rare diseases including microcystic lymphatic malformations, venous malformations and angiofibromas. The products are being developed using Quoin’s in-licensed proprietary Invisicare delivery technology. There are currently no FDA approved treatments for either microcystic lymphatic malformations or venous malformations. The proprietary Invisicare delivery technology, which Quoin has exclusive rights to for all orphan rare skin disease applications, is designed to optimize penetration of rapamycin deep into dermis where it can be most effective clinically. The Invisicare technology is also being utilized in Quoin’s QRX003 topical lotion, which is in late-stage clinical testing as a potential treatment for Netherton Syndrome, a rare genetic disease. Quoin believes QRX003 has the potential to become the first approved treatment for this disease. “As we continue to advance the clinical development of Quoin’s lead product, QRX003, for Netherton Syndrome, we are pleased to announce the filing of this patent and the initiation of the development of our novel formulations as potential treatments for these additional rare skin diseases. By combining the known clinical activity of rapamycin with this optimized delivery system, we believe our novel topical formulations may have the potential to effectively treat these diseases. We have seen other topical formulations of rapamycin underperform in clinical settings across a number of indications, which we believe may be as a result of suboptimal delivery of the drug at the target sites. The Invisicare technology is designed to overcome these limitations. We are now moving forward with our plans to submit IND applications for at least two of these target indications this year and to formally initiating clinical development as soon as possible ” said Dr. Michael Myers, Chief Executive Officer of Quoin. Quoin is currently enrolling patients in three clinical trials being conducted under its open Investigational New Drug (IND) application, evaluating its QRX003 topical lotion as a potential treatment of Netherton Syndrome. To date, Quoin remains the only company actively recruiting subjects into multiple NS clinical trials that are being conducted under an open IND. To find out more about Quoin’s clinical studies relating to Netherton Syndrome, please visit http://www.nethertonsyndromeclinicaltrials.com/. About Microcystic Lymphatic Malformations Microcystic lymphatic malformation is one subtype of lymphatic malformation (LM), a congenital malformation of the lymphatic vessels in soft tissues, including the skin. LM is classified into the macrocystic type, cysts larger than 2 cm with clear margins (previously known as cystic hygromas), and the microcystic type, consisting of cysts smaller than 2 cm, that appear diffuse, and grow without clear borders (previously known as lymphangioma circumscriptum). When the two types concur it is called the combined type. Microcystic lesions are commonly found inside the mouth, throat, and in the tongue, parotid gland and submandibular gland. Symptoms include deformity, and problems with breathing and feeding. The exact cause is unknown but is likely related to a malformation of the lymphatic system at six to ten weeks of gestation, when some lymphatic tissue fails to communicate with the lymphatic and venous system.1 Lymphatic malformations occurring in 1 in 6000 to 16,000 patients. 2 About Venous Malformations Venous malformation (VM) is the most common type of congenital vascular malformation (CVM) with an incidence of 1 to 2 in 10,000 and a prevalence of 1%. They can cause significant morbidity, pain and discomfort to patients as they can lead to serious local and systemic complications. Although present at birth, they are not always clinically evident until later in life and tend to grow in concert with the child and without spontaneous regression. VMs are composed of ectatic venous channels found usually in the head, neck, limbs, and trunk and are thought to be sporadic in most cases, though familial inheritance patterns exist. Accurate diagnosis has been a limiting factor in VM management. An increased emphasis has been placed on creating comprehensive classification systems for diagnostic and therapeutic purposes of this chronic condition. Doppler ultrasound (US) and magnetic resonance imaging (MRI) are key imaging methods used to characterize and diagnose VMs. Treatment options include surgery, sclerotherapy, and ablative therapies. 3 About Angiofibroma Cutaneous angiofibroma is a benign skin tumor characterized by fibrovascular tissue and presents as a group of lesions with varied clinical appearances but consistent histological features. These benign fibrous neoplasms exhibit a proliferation of stellate and spindled cells, thin-walled blood vessels with dilated lumina in the dermis, and concentric collagen bundles. These growths typically manifest as small, firm, reddish, or flesh-colored papules, most commonly on the face (often referred to as fibrous papules or adenoma sebaceum), particularly around the nose and cheeks.4 About Quoin Pharmaceuticals Ltd. Quoin Pharmaceuticals Ltd. is a clinical-stage specialty pharmaceutical company focused on developing and commercializing therapeutic products that treat rare and orphan diseases. We are committed to addressing unmet medical needs for patients, their families, communities and care teams. Quoin’s innovative pipeline comprises four products in development that collectively have the potential to target a broad number of rare and orphan indications, including Netherton Syndrome, Peeling Skin Syndrome, Palmoplantar Keratoderma, Scleroderma, Epidermolysis Bullosa and others. For more information, go to: www.quoinpharma.com. Cautionary Note Regarding Forward-Looking Statements The Company cautions that statements in this press release that are not descriptions of historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words referencing future events or circumstances such as “expect,” “intend,” “hope,” “plan,” “potential,” “anticipate,” “look forward,” “believe,” “may,” and “will,” among others. All statements that reflect the Company’s expectations, assumptions, projections, beliefs, or opinions about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements relating to: the Company’s new U.S. and International patent applications for novel topical rapamycin (sirolimus) formulations as potential treatments for a number of rare diseases including microcystic lymphatic malformations, venous malformations and angiofibromas; Invisicare delivery technology being designed to optimize penetration of rapamycin deep into dermis where it can be most effective clinically; the potential efficacy of QRX003 as a treatment for Netherton Syndrome; the progress or success of Quoin’s ongoing clinical trials; combining rapamycin with the Invisicare technology delivery system having the potential to effectively treat these diseases; plans to submit IND applications for at least two of these target indications this year and initiating clinical development as soon as possible; and Quoin’s products in development collectively having the potential to target a broad number of rare and orphan indications, including Netherton Syndrome, Peeling Skin Syndrome, Palmoplantar Keratoderma, Scleroderma, Epidermolysis Bullosa and others. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These forward-looking statements are based upon the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties including, but not limited to, the Company’s ability to protect its assets with the new patent applications; the Company’s ability to obtain regulatory approvals for the commercialization of its product candidates or to comply with ongoing regulatory requirements; the Company’s ability to deliver a safe and effective treatment for Netherton Syndrome; the Company may be unable to submit applications and initiate clinical development as and when planned; and other factors discussed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023 and in other filings the Company has made and may make with the SEC in the future. One should not place undue reliance on these forward-looking statements, which speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as may be required by law. For further information, contact: Quoin Pharmaceuticals Ltd. Michael Myers, Ph.D., CEO mmyers@quoinpharma.com Investor Relations PCG Advisory Jeff Ramson jramson@pcgadvisory.com (646) 863-6341 1 Microcystic lymphatic malformation | About the Disease | GARD 2 Genetic and Molecular Determinants of Lymphatic Malformations: Potential Targets for Therapy - PMC 3 Venous malformations: clinical diagnosis and treatment - PMC 4 Cutaneous Angiofibroma - StatPearls - NCBI Bookshelf

IRVINE, Calif., Oct. 23, 2023 (GLOBE NEWSWIRE) -- Eledon Pharmaceuticals, Inc. (“Eledon”) (NASDAQ: ELDN) today announced the appointment of Eliezer Katz, M.D., FACS as Chief Medical Officer with responsibility for leading the company’s clinical development programs. “We are pleased to welcome Dr. Katz to the Eledon team,” said David-Alexandre C. Gros, M.D., Eledon Chief Executive Officer. “Dr. Katz brings a wealth of knowledge in the surgical transplantation field together with extensive experience designing and overseeing clinical trials for immunosuppressive treatments. We look forward to his leadership and contributions as we continue to advance tegoprubart for the prevention of rejection in patients undergoing transplantation procedures.” Dr. Katz is an experienced transplant surgeon with significant clinical development experience. Most recently, he was Chief Medical Officer at eGenesis where he helped lead the clinical development of eGenesis’ xenotransplantation programs. Prior to eGenesis, Dr. Katz was Vice President of Clinical Development first at Viela Bio and then at Horizon Therapeutics following its acquisition of Vielo Bio. At Horizon and Viela Bio, Dr. Katz led the clinical development of inebilizumab in multiple autoimmune indications and oversaw the regulatory submission and approval of UPLIZNA®(inebilizumab) to treat neuromyelitis optica spectrum disorder in adults. Prior to Viela Bio, Dr. Katz served as Senior Director of Clinical Development at MedImmune Inc. where he oversaw the clinical development of three different biologics. Prior to MedImmune, Dr. Katz served as Senior Director of Transplantation with the Medicine Development Group at Pfizer. At Pfizer, he oversaw multiple research programs with rapamycin, an anti-rejection drug, and was instrumental in the regulatory submission and FDA approval of rapamycin as a treatment for lymphangioleiomyomatosis (LAM), a rare and fatal lung disease. Before joining industry, Dr. Katz spent two decades as a transplant surgeon. He was director of the abdominal transplantation division at Integris Baptist Medical Center in Oklahoma City, and an associate professor of surgery and the director of the liver transplantation division at the University of Massachusetts Medical Center, Worcester, MA. Dr. Katz spearheaded liver transplantation advances at these institutions and was actively involved with policy making in organ donation and allocation. Dr. Katz earned his M.D. at Hadassah Hebrew University Medical School in Jerusalem. “With tegoprubart, Eledon is well positioned to meet the critical need for innovative transplantation immunosuppressant therapies,” said Dr. Katz. “I’m excited to join Eledon as the company continues to realize its vision to significantly improve the functional life of transplanted organs and address the side effects of current immunosuppressive treatments.” About Eledon Pharmaceuticals and tegoprubart Eledon Pharmaceuticals is a clinical stage biotechnology company with immunology expertise that is developing therapies to protect and prevent rejection of transplanted organs, as well as to treat amyotrophic lateral sclerosis (ALS). The Company’s lead compound in development is tegoprubart, an anti-CD40L antibody with high affinity for CD40 Ligand, a well-validated biological target with broad therapeutic potential. Eledon is headquartered in Irvine, California. For more information, please visit the company’s website at www.eledon.com. Follow Eledon Pharmaceuticals on social media: LinkedIn; Twitter Investor Contact: Stephen JasperGilmartin Group(858) 525 2047stephen@gilmartinir.com Media Contact: Jenna UrbanBerry & Company Public Relations(212) 253 8881jurban@berrypr.com Source: Eledon Pharmaceuticals

A new study uses single cell analysis of gene expression combined with spatial transcriptomics to reveal previous unrecognized immune cell types and interactions within adipose tissue. Fat tissue, for as much as it's been vilified, is an incredibly complex and essential bodily organ involved in energy storage and hormone production, among other functions. Yet, modern lifestyles have led to a worldwide epidemic of obesity, and a corresponding increase in related conditions like type 2 diabetes and cardiovascular disease. Researchers are attempting to uncover the basics of how fat tissue is structured and, specifically, inflammation associated with obesity, in the hopes of unlocking the connection between the accumulation of fat and poor health outcomes. A new study from Lindsey Muir, Ph.D., Ph.D.-candidate Cooper Stansbury, and their colleagues uses single cell analysis of gene expression combined with spatial transcriptomics to reveal previous unrecognized immune cell types and interactions within adipose tissue. Spatial transcriptomics is a newer technology that captures all gene expression in small spots across an entire thin section of tissue. Studying fat is easier said than done. In tissues that are organized into defined layers for example the spinal cord or the brain "it's easier to do sanity checks with your data and identify this or that layer as a particular cell type and know that it should be expressing genes X, Y, and Z," said Muir, a research assistant professor in the Department of Computational Medicine and Bioinformatics. "With adipose, it's a lot more challenging because the cell types are distributed evenly throughout the tissue, without defined cell layers." In obesity, fat cells, or adipocytes, expand and can reach a limit that ultimately causes cell death and leads to inflammation. To better understand the types of immune cells within adipose tissue and where they are in relation to each other in obesity, the team fed mice a high fat diet over the course of 14 weeks, collected fat tissue, and then used single cell and spatial analyses to produce a read out of all the mRNAs present in the sample. Using a computational process known as clustering in the single cell data, they were able to group cells whose genetic makeup more closely resembled each other than other groups or the overall sample. They discovered something surprising about the samples' population of macrophages, an immune cell whose job it is to clean up dead cells and debris. "We knew going in that macrophages would likely have multiple subtypes… what surprised us were the number that came out that were highly different from each other and coming up at different times and becoming more dominant over time." They identified five types, which they named Mac1, 2, 3, 4, and 5. Mac1 were resident to the tissue in both lean mice on a normal diet and obese mice. Mac2 and Mac3, which were identified by their pro-inflammatory genes, peaked after 8 weeks of the high-fat diet. However, as the high-fat diet progressed to 14 weeks, Mac4 and Mac5 cells, which had low pro-inflammatory gene expression, predominated, while pro-inflammatory Mac2 and Mac3 cells decreased. "The thinking in the field has been that the type of macrophages that accumulate in obesity are promoting an inflammatory state. Based on these data there's a lot more to the story," said Muir. Her hypothesis is that Mac4 and Mac5 are the lipid associated macrophages (LAMs) described in her own prior work and by other researchers and may be a sign of the body attempting to quell a damaging level of inflammation from pro-inflammatory macrophages and dying adipocytes. Next, painstakingly careful sectioning of fresh frozen fat tissue enabled analysis by spatial transcriptomics. Each analysis spot in the spatial method has a unique barcode that attaches to the mRNA in the tissue on top of that spot, so gene expression can later be mapped to specific locations in the tissue using the barcodes as coordinates. In this method, the sections are also imaged just prior to collection of mRNA. The study examined these images looking for tell-tale markers called crown-like structures -- structures that are associated with insulin resistance. "Once crown-like structures appear, it takes them a long time to go away and their appearance indicates tissue dysfunction," noted Muir. "Using image processing, we identified based on the density of these regions what was likely to be a crown-like structure and then went in to verify that we could see them visually," said Muir. These structures had gene expression indicating the presence of Mac4 and Mac5 LAMs. With more insight into the cellular makeup and spatial organization of fat tissue in the context of obesity, the next step, Muir said, is to examine the signaling processes and proteins associated with the development of LAMs and metabolic disorders.